Immunogenicity and Safety of Different Vaccination Schedules of Tetravalent Dengue Vaccine in Healthy Subjects 9 to 50 Years of Age

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The aim of the study is to assess the immune response and the safety of different vaccination schedules of CYD dengue vaccine.

The primary objectives of the study are:

To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule, in previously dengue exposed participants 28 days after the last injection.

To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule compared to the immune response elicited by CYD vaccine given as a 3-dose schedule in previously dengue exposed participants, 1 year after the last injection.

To demonstrate the non-inferiority of the immune response elicited against each dengue serotype elicited by a booster dose of CYD dengue vaccine one year or two years after the last injection in the primary series in previously dengue exposed participants.

The secondary objectives of the study are:

To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule, in previously dengue exposed participants 28 days after the last injection.

To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule, in previously dengue exposed participants, one year after the last injection.

To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 3 to the antibody levels immediately before receiving a booster dose, by baseline dengue serostatus.

To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 2 and 28 days post-injection 3 from Group 1 in a primary series schedule by baseline dengue serostatus.

To demonstrate the superiority of the immune response elicited against each dengue serotype 28 days after administration of a booster dose of CYD dengue vaccine, in previously dengue exposed participants, at One year or two years after last injection in the primary series.

To describe the seroconversion rate 28 days post-booster injection in all 3 groups.

To describe all hospitalized virologically confirmed dengue (VCD) cases during the study.

To evaluate the safety profile of CYD after each and any injection during the trial. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.

Condition or disease

Intervention/treatment

Phase

Dengue FeverDengue Hemorrhagic Fever

Biological: CYD Dengue VaccineBiological: Placebo (NaCl 0.9%)

Phase 2

Detailed Description:

Healthy participants aged between 9 and 50 year receive CYD dengue vaccine in various schedules, in two sequential stages. In the first stage, participants receive 1, 2 or 3 injections of CYD dengue vaccine over a 12-month period. In the second stage, participants are randomized to receive a booster dose of CYD dengue vaccine at either 12 months or 24 months after the third injection of study vaccine. Only participants who were previously dengue exposed at baseline (dengue seropositive) are eligible to receive the booster dose.

Immunogenicity and Safety of Tetravalent Dengue Vaccine Given in 1 , 2 , or 3 Dose Schedules (STAGE I) Followed by a Single Booster Injection of the Same Vaccine (STAGE II) 1 or 2 Years After the Last Primary Dose in Healthy Subjects 9 to 50 Years of Age in Colombia and the Philippines

3 injections of CYD dengue vaccine at Day 0, Day 0 + 6 months, and Day 0 + 12 months. Booster injection of CYD dengue vaccine 1 year or 2 years after third injection among previously dengue exposed participants only.

Biological: CYD Dengue Vaccine

0.5 mL, Subcutaneous

Experimental: Group 2

1 injection of placebo (NaCl 0.9%) followed by 2 injections of CYD dengue vaccine at Day 0, Day 0 + 6 months, and Day 0 + 12 months. Booster injection of CYD dengue vaccine 1 year or 2 years after third injection among previously dengue exposed participants only.

Biological: CYD Dengue Vaccine

0.5 mL, Subcutaneous

Biological: Placebo (NaCl 0.9%)

0.5 mL, Subcutaneous

Experimental: Group 3

2 injections of placebo (NaCl 0.9%) followed by 1 injection of CYD dengue vaccine at Day 0, Day 0 + 6 months, and Day 0 + 12 months. Booster injection of CYD dengue vaccine 1 year or 2 years after third injection among previously dengue exposed participants only.

Neutralizing antibody titers against each dengue virus serotype 28 days after the last CYD dengue injection in the Group 1 and Group 2 primary series [ Time Frame: 28 days after the last CYD dengue vaccine injection in primary series ]

Neutralizing antibody titers against each dengue virus serotype 1 year after the last injection in the Group 1 and Group 2 primary series [ Time Frame: 1 year after the last CYD dengue vaccine injection in the primary series ]

Neutralizing antibody levels are measured using dengue PRNT.

Neutralizing antibody titers against each dengue virus serotype 28 days after the booster dose at 1 year or 2 years after the last CYD dengue vaccine injection in the primary series [ Time Frame: 28 days after the booster dose ]

Neutralizing antibody levels are measured using dengue PRNT.

Secondary Outcome Measures :

Neutralizing antibody titers against each dengue virus serotype 28 days post-injection 2 in Group 1, 28 days post-injection 3, and 1 year post-injection 3 in all 3 groups [ Time Frame: : 28 days and 1 year post-injection 3 ]

Neutralizing antibody levels are measured using dengue PRNT. The level of antibodies are assessed after the second injection of CYD dengue vaccine in Group 1, 28 days post-injection 3 and 1 year post-injection 3 in all 3 groups.

Neutralizing antibody titers against each dengue virus serotype before the booster dose [ Time Frame: Immediately before administration of the booster dose (1 year or 2 years after last CYD dengue vaccine injection) ]

Neutralizing antibody levels are measured using dengue PRNT.

Percentage of participants with seroconversion against each dengue virus serotype [ Time Frame: Immediately prior to and 28 days after the booster dose ]

Seroconversion is assessed as percentages of participants with either a pre-booster titer < 10 (1/dil) and a post-booster titer ≥ 40 (1/dil), or a pre-booster titer ≥ 10 (1/dil) and a ≥ 4 fold increase in post-booster titer.

Number of Participants With Solicited Injection Site Reactions [ Time Frame: Within 7 days after vaccination ]

Solicited injection site reactions: Pain, Erythema, and Swelling.

Number of Participants With Solicited Systemic Reactions [ Time Frame: Within 14 days after vaccination ]

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Layout table for eligibility information

Ages Eligible for Study:

9 Years to 50 Years (Child, Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Aged 9 to 50 years on the day of enrollment

Subject in good health, based on medical history and physical examination

Assent form or informed consent form (ICF) has been signed and dated by the subject (based on local regulations), and ICF has been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations)

Subject and parent(s)/legally acceptable representative(s) able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination)

Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device or medical procedure

Self-reported or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)

Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances

Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion

Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response

Planned receipt of any vaccine in the 4 weeks following any trial vaccination

Previous vaccination against dengue disease with either the trial vaccine or another vaccine

Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily

Current alcohol abuse or drug addiction that, based on investigator's judgment, may interfere with the subject´s ability to comply with trial procedures.

Identified as a site employee of the Investigator, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e. ,immediate, husband, wife, and their children, adopted or natural) of the employees or the Investigator

A prospective subject must not be included in the study until the following conditions and/or symptoms are resolved:

Febrile illness (temperature ≥ 38.0°C) or moderate or severe acute illness/infection (according to Investigator's judgment) on the day of vaccination.

Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.

Individual participant data (IPD) and supporting clinical documents are available for request at www.clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: Clinicalstudydatarequest.com/Sanofi.